A number of patents describe coating compositions and pellets coated therewith which are adaptable for oral administration to ruminants. The coating protects the core material of the pellets in the rumen and releases it postruminally. The coating is composed of a specific mixture of a film-forming polymeric material (I) and hydrophobic material (II), (I) and a flake material (III), or (I) and (II) and (III). Some bioactive substances, which are miscible with the basic coating polymer, can be dispersed molecularly in the polymer matrix to achieve the desirable post-ruminal delivery. U.S. patents of interest include U.S. Pat. Nos. 3,619,200; 3,880,990; 3,041,243; 3,697,640; 3,988,480; 3,383,283; 3,275,518; 3,623,997; 3,073,748; 3,829,564; 3,832,252; and 3,917,813. Of particular interest are U.S. Pat. Nos. 4,181,708; 4,181,709; 4,181,710; 4,837,004; 4,808,412; 4,717,567; and 4,595,584.
These patents only describe applications for ruminants. No non-ruminant application is disclosed.
U.S. Pat. No. 3,041,243 (1962) describes the art of sealing coat for tablets and the like. A copolymer of vinylpyridine and styrene is described in the patent. Powdered filler is added during the intermediate drying after the application of each coating so as to minimize the agglomeration during the coating process. GB Pat. No. 888,131 describes a method for preparing solid, oral medicament forms, e.g., tablets, prills and granules protecting from the action of moisture and/or oxygen by a water-insoluble, acid-soluble coating of a film-forming polymer selected from poly-2-vinylpyridine, poly-4-vinylpyridine, poly-2-methyl-5-vinylpyridine, poly-5-ethyl-2-vinylpyridine and copolymers containing at least 50% by weight of these and a comonomer such as vinyl acetate, acrylonitrile, methyl acrylate and styrene. These two patents do not describe any purification method to remove monomers and oligomers from copoly(VP/ST), nor do the patents describe functional additives which in combination with the polymer form a coating composition.
U.S. Pat. No. 4,443,497 (1984) describes a method of preparing microcapsules by conducting the phase separation of a coating polymer material in the presence of ethylcellulose. The steps include a) dissolving a coating material and ethylcellulose in a solvent, b) dispersing drug particles to the solution, c) adding to the dispersion an organic liquid which is miscible to the solvent and which is nonsolvent for said coating polymer material and the core material, thereby forming coating walls of said coating polymer material on and around the particles, and then c) recovering the thus-formed microcapsules therefrom. Ethylcellulose present in the phase separation system minimizes the coagulation of the coating polymer material. The examples of the wall forming material which can be used in the patent art include a water-insoluble, acid-soluble coating polymer material (i.e., a coating polymer material soluble in water at a pH not higher than 5).
U.S. Pat. No. 4,486,471 describes a process for making gastric release pharmaceutical microcapsules in which the wall material consists of ethylcellulose and a water-insoluble, acid-soluble polymer material. The process steps include a) dissolving ethylcellulose in a solvent, b) dispersing drug particles in the solution, c) cooling the dispersion in the presence of a water-insoluble, acid-soluble polymer material until the ethylcellulose separates out from the dispersion to form coating walls on and around the particles of said core material, and then d) recovering the thus-formed microcapsules therefrom. Active substance is rapidly released in contact with gastric juice on account of dissolution of the acid-soluble polymer material to render the microcapsule wall porous.
U.S. Pat. No. 4,533,562 describes a method of preparing coated solid preparation without the use of solvents, with a powdered film-forming polymer and with a liquid plasticizer having an affinity for the polymer. The polymers useful in the patent include polymers soluble in the stomach such as vinylpyridine/methyl acrylate methacrylate copolymer.
Japanese Pat. No. JP 70,002,031 describes a method for preparing enteric coated tablets comprising press-coating solid tablets by the use of a coating composition comprised of (i) an enteric material and (ii) an enteric material which does not swell in the gastric juice but dissolves in the gastric juice.
Another Japanese Pat. No., JP 64,017,167, describes a process for coating pharmaceutical tablets for oral administration with a water-insoluble amphoteric polymer which is soluble in acids and alkalines. The tablets or granules coated with the polymer are indefinitely stable in a moist atmosphere but rapidly disintegrate in gastric and intestinal juice with release of the medicament.
Another Japanese Pat. No., JP 69,011,915, describes a method for making capsules suitable for release of medicament in gastric juice. The medicament is coated with an acid-soluble polymer and one or two polymeric resins soluble in gastric and/or intestinal juices.
To be useful for human applications, the polymeric materials must be essentially free from or containing reasonably low residual monomers so that the polymeric materials would not cause any safety concern.
European Pat. No. 281,464describes a purification process for removing residual monomers from styrene/vinylpyridine copolymers by selective extraction with super critical carbon dioxide gas. The process gives copolymers containing 1 ppm residual monomers.
U.S. Pat. Nos. 4,429,113 and 4,518,769 describe processes for separating high molecular weight fraction from polar polymer using polyfunctional acid or base coascervating agent to form crosslinked, coacervated polymer solids.
Another patent application no., EP 176642 A1, describes an acetic acid wash process for purifying vinylpyridine copolymers.
U.S. Pat. No. 3,718,631 describes a purification method employing extraction with pyridine in xylene.